Influence of deep sternal wound infection on long-term survival after cardiac surgery

BACKGROUND: This study aimed to investigate the influence of deep sternal wound infection on long-term survival following cardiac surgery. MATERIAL AND METHODS: In our institutional database we retrospectively evaluated medical records of 4732 adult patients who received open-heart surgery from January 1995 through December 2005. The predictive factors for DSWI were determined using logistic regression analysis. Then, each patient with deep sternal wound infection (DSWI) was matched with 2 controls without DSWI, according to the risk factors identified previously. After checking balance resulting from matching, short-term mortality was compared between groups using a paired test, and long-term survival was compared using Kaplan-Meier analysis and a Cox proportional hazard model. RESULTS: Overall, 4732 records were analyzed. The mean age of the investigated population was 69.3±12.8 years. DSWI occurred in 74 (1.56%) patients. Significant independent predictive factors for deep sternal infections were active smoking (OR 2.19, CI95 1.35-3.53, p=0.001), obesity (OR 1.96, CI95 1.20-3.21, p=0.007), and insulin-dependent diabetes mellitus (OR 2.09, CI95 1.05-10.06, p=0.016). Mean follow-up in the matched set was 125 months, IQR 99-162. After matching, in-hospital mortality was higher in the DSWI group (8.1% vs. 2.7% p=0.03), but DSWI was not an independent predictor of long-term survival (adjusted HR 1.5, CI95 0.7-3.2, p=0.33). CONCLUSIONS: The results presented in this report clearly show that post-sternotomy deep wound infection does not influence long-term survival in an adult general cardio-surgical patient population.

Periodontal and general health in long-term periodontal maintenance patients treated in a Norwegian private practice: a descriptive report from a compliant and partially compliant survivor population

BACKGROUND There is weak evidence to support the benefit of periodontal maintenance therapy in preventing tooth loss. In addition, the effects of long-term periodontal treatment on general health are unclear. METHODS Patients who were compliant and partially compliant (15 to 25 years' follow-up) in private practice were observed for oral and systemic health changes. RESULTS A total of 219 patients who were compliant (91 males and 128 females) were observed for 19.1 (range 15 to 25; SD ± 2.8) years. Age at reassessment was 64.6 (range: 39 to 84; SD ± 9.0) years. A total of 145 patients were stable (0 to 3 teeth lost), 54 were downhill (4 to 6 teeth lost), and 21 patients extreme downhill (>6 teeth lost); 16 patients developed hypertension, 13 developed type 2 diabetes, and 15 suffered myocardial infarcts (MIs). A minority developed other systemic diseases. Risk factors for MI included overweight (odds ratio [OR]: 9.04; 95% confidence interval [CI]: 2.9 to 27.8; P = 0.000), family history with cardiovascular disease (OR: 3.10; 95% CI: 1.07 to 8.94; P = 0.029), type 1 diabetes at baseline (P = 0.02), and developing type 2 diabetes (OR: 7.9; 95% CI: 2.09 to 29.65; P = 0.000). A total of 25 patients who were partially compliant (17 males and eight females) were observed for 19 years. This group had a higher proportion of downhill and extreme downhill cases and MI. CONCLUSIONS Patients who left the maintenance program in a periodontal specialist practice in Norway had a higher rate of tooth loss than patients who were compliant. Patients who were compliant with maintenance in a specialist practice in Norway have a similar risk of developing type 2 diabetes as the general population. A rate of 0.0037 MIs per patient per year was recorded for this group. Due to the lack of external data, it is difficult to assess how this compares with patients who have periodontal disease and are untreated.

Impact of stent overlap on long-term clinical outcomes in patients treated with newer-generation drug-eluting stents

Aims: Early-generation drug-eluting stent (DES) overlap (OL) is associated with impaired long-term clinical outcomes whereas the impact of OL with newer-generation DES is unknown. Our aim was to assess the impact of OL on long-term clinical outcomes among patients treated with newer-generation DES. Methods and results: We analysed the three-year clinical outcomes of 3,133 patients included in a prospective DES registry according to stent type (sirolimus-eluting stents [SES; N=1,532] versus everolimus-eluting stents [EES; N=1,601]), and the presence or absence of OL. The primary outcome was a composite of death, myocardial infarction (MI), and target vessel revascularisation (TVR). The primary endpoint was more common in patients with OL (25.1%) than in those with multiple DES without OL (20.8%, adj HR=1.46, 95% CI: 1.03-2.09) and patients with a single DES (18.8%, adj HR=1.74, 95% CI: 1.34-2.25, p<0.001) at three years. A stratified analysis by stent type showed a higher risk of the primary outcome in SES with OL (28.7%) compared to other SES groups (without OL: 22.6%, p=0.04; single DES: 17.6%, p<0.001), but not between EES with OL (22.3%) and other EES groups (without OL: 18.5%, p=0.30; single DES: 20.4%, p=0.20). Conclusions: DES overlap is associated with impaired clinical outcomes during long-term follow-up. Compared with SES, EES provide similar clinical outcomes irrespective of DES overlap status.

Comparison of iron isotope variations in modern and Ordovician siliceous Fe oxyhydroxide deposits

Formation pathways of ancient siliceous iron formations and related Fe isotopic fractionation are still not completely understood. Investigating these processes, however, is difficult as good modern analogues to ancient iron formations are scarce. Modern siliceous Fe oxyhydroxide deposits are found at marine hydrothermal vent sites, where they precipitate from diffuse, low temperature fluids along faults and fissures on the seafloor. These deposits exhibit textural and chemical features that are similar to some Phanerozoic iron formations, raising the question as to whether the latter could have precipitated from diffuse hydrothermal fluids rather than from hydrothermal plumes. In this study, we present the first data on modern Fe oxyhydroxide deposits from the Jan Mayen hydrothermal vent fields, Norwegian-Greenland Sea. The samples we investigated exhibited very low δ56Fe values between -2.09‰ and -0.66‰. Due to various degrees of partial oxidation, the Fe oxyhydroxides are with one exception either indistinguishable from low-temperature hydrothermal fluids from which they precipitated (-1.84‰ and -1.53‰ in δ56Fe) or are enriched in the heavy Fe isotopes. In addition, we investigated Fe isotope variations in Ordovician jasper beds from the Løkken ophiolite complex, Norway, which have been interpreted to represent diagenetic products of siliceous ferrihydrite precursors that precipitated in a hydrothermal plume, in order to compare different formation pathways of Fe oxyhydroxide deposits. Iron isotopes in the jasper samples have higher δ56Fe values (-0.38‰ to +0.89‰) relative to modern, high-temperature hydrothermal vent fluids (ca. -0.40‰ on average), supporting the fallout model. However, formation of the Ordovician jaspers by diffuse venting cannot be excluded, due to lithological differences of the subsurface of the two investigated vent systems. Our study shows that reliable interpretation of Fe isotope variations in modern and ancient marine Fe oxyhydroxide deposits depends on comprehensive knowledge of the geological context. Furthermore, we demonstrate that very negative δ56Fe values in such samples might not be the result of microbial dissimilatory iron reduction, but could be caused instead by inorganic reactions.

Quantitative Myocardial Contrast Echocardiography during Pharmacological Stress for Diagnosis of Coronary Artery Disease: A Systematic Review and Meta-analysis of Diagnostic Accuracy Studies

AIMS: We conducted a meta-analysis to evaluate the accuracy of quantitative stress myocardial contrast echocardiography (MCE) in coronary artery disease (CAD). METHODS AND RESULTS: Database search was performed through January 2008. We included studies evaluating accuracy of quantitative stress MCE for detection of CAD compared with coronary angiography or single-photon emission computed tomography (SPECT) and measuring reserve parameters of A, beta, and Abeta. Data from studies were verified and supplemented by the authors of each study. Using random effects meta-analysis, we estimated weighted mean difference (WMD), likelihood ratios (LRs), diagnostic odds ratios (DORs), and summary area under curve (AUC), all with 95% confidence interval (CI). Of 1443 studies, 13 including 627 patients (age range, 38-75 years) and comparing MCE with angiography (n = 10), SPECT (n = 1), or both (n = 2) were eligible. WMD (95% CI) were significantly less in CAD group than no-CAD group: 0.12 (0.06-0.18) (P < 0.001), 1.38 (1.28-1.52) (P < 0.001), and 1.47 (1.18-1.76) (P < 0.001) for A, beta, and Abeta reserves, respectively. Pooled LRs for positive test were 1.33 (1.13-1.57), 3.76 (2.43-5.80), and 3.64 (2.87-4.78) and LRs for negative test were 0.68 (0.55-0.83), 0.30 (0.24-0.38), and 0.27 (0.22-0.34) for A, beta, and Abeta reserves, respectively. Pooled DORs were 2.09 (1.42-3.07), 15.11 (7.90-28.91), and 14.73 (9.61-22.57) and AUCs were 0.637 (0.594-0.677), 0.851 (0.828-0.872), and 0.859 (0.842-0.750) for A, beta, and Abeta reserves, respectively. CONCLUSION: Evidence supports the use of quantitative MCE as a non-invasive test for detection of CAD. Standardizing MCE quantification analysis and adherence to reporting standards for diagnostic tests could enhance the quality of evidence in this field.

CRTC2 polymorphism as a risk factor for the incidence of metabolic syndrome in patients with solid organ transplantation.

Metabolic syndrome after transplantation is a major concern following solid organ transplantation (SOT). The CREB-regulated transcription co-activator 2 (CRTC2) regulates glucose metabolism. The effect of CRTC2 polymorphisms on new-onset diabetes after transplantation (NODAT) was investigated in a discovery sample of SOT recipients (n1=197). Positive results were tested for replication in two samples from the Swiss Transplant Cohort Study (STCS, n2=1294 and n3=759). Obesity and other metabolic traits were also tested. Associations with metabolic traits in population-based samples (n4=46'186, n5=123'865, n6>100,000) were finally analyzed. In the discovery sample, CRTC2 rs8450-AA genotype was associated with NODAT, fasting blood glucose and body mass index (Pcorrected<0.05). CRTC2 rs8450-AA genotype was associated with NODAT in the second STCS replication sample (odd ratio (OR)=2.01, P=0.04). In the combined STCS replication samples, the effect of rs8450-AA genotype on NODAT was observed in patients having received SOT from a deceased donor and treated with tacrolimus (n=395, OR=2.08, P=0.02) and in non-kidney transplant recipients (OR=2.09, P=0.02). Moreover, rs8450-AA genotype was associated with overweight or obesity (n=1215, OR=1.56, P=0.02), new-onset hyperlipidemia (n=1007, OR=1.76, P=0.007), and lower high-density lipoprotein-cholesterol (n=1214, β=-0.08, P=0.001). In the population-based samples, a proxy of rs8450G>A was significantly associated with several metabolic abnormalities. CRTC2 rs8450G>A appears to have an important role in the high prevalence of metabolic traits observed in patients with SOT. A weak association with metabolic traits was also observed in the population-based samples.The Pharmacogenomics Journal advance online publication, 8 December 2015; doi:10.1038/tpj.2015.82.

Bone mineral density (BMD) and vertebral trabecular bone score (TBS) for the identification of elderly women at high risk for fracture: the SEMOF cohort study

PURPOSE To determine the predictive value of the vertebral trabecular bone score (TBS) alone or in addition to bone mineral density (BMD) with regard to fracture risk. METHODS Retrospective analysis of the relative contribution of BMD [measured at the femoral neck (FN), total hip (TH), and lumbar spine (LS)] and TBS with regard to the risk of incident clinical fractures in a representative cohort of elderly post-menopausal women previously participating in the Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk study. RESULTS Complete datasets were available for 556 of 701 women (79 %). Mean age 76.1 years, LS BMD 0.863 g/cm(2), and TBS 1.195. LS BMD and LS TBS were moderately correlated (r (2) = 0.25). After a mean of 2.7 ± 0.8 years of follow-up, the incidence of fragility fractures was 9.4 %. Age- and BMI-adjusted hazard ratios per standard deviation decrease (95 % confidence intervals) were 1.58 (1.16-2.16), 1.77 (1.31-2.39), and 1.59 (1.21-2.09) for LS, FN, and TH BMD, respectively, and 2.01 (1.54-2.63) for TBS. Whereas 58 and 60 % of fragility fractures occurred in women with BMD T score ≤-2.5 and a TBS <1.150, respectively, combining these two thresholds identified 77 % of all women with an osteoporotic fracture. CONCLUSIONS Lumbar spine TBS alone or in combination with BMD predicted incident clinical fracture risk in a representative population-based sample of elderly post-menopausal women.

The muscarinic antagonists scopolamine and atropine are competitive antagonists at 5-HT3 receptors

Scopolamine is a high affinity muscarinic antagonist that is used for the prevention of post-operative nausea and vomiting. 5-HT3 receptor antagonists are used for the same purpose and are structurally related to scopolamine. To examine whether 5-HT3 receptors are affected by scopolamine we examined the effects of this drug on the electrophysiological and ligand binding properties of 5-HT3A receptors expressed in Xenopus oocytes and HEK293 cells, respectively. 5-HT3 receptor-responses were reversibly inhibited by scopolamine with an IC50 of 2.09 μM. Competitive antagonism was shown by Schild plot (pA2 = 5.02) and by competition with the 5-HT3 receptor antagonists [3H]granisetron (Ki = 6.76 µM) and G-FL (Ki = 4.90 µM). The related molecule, atropine, similarly inhibited 5-HT evoked responses in oocytes with an IC50 of 1.74 µM, and competed with G-FL with a Ki of 7.94 µM. The reverse experiment revealed that granisetron also competitively bound to muscarinic receptors (Ki = 6.5 µM). In behavioural studies scopolamine is used to block muscarinic receptors and induce a cognitive deficit, and centrally administered concentrations can exceed the IC50 values found here. It is therefore possible that 5-HT3 receptors are also inhibited. Studies that utilise higher concentrations of scopolamine should be mindful of these potential off-target effects.

Genetic Predictors of Clinical Outcomes in Non-Small Cell Lung Cancer Patients

Lung cancer is the leading cause of cancer-related mortality in the US. Emerging evidence has shown that host genetic factors can interact with environmental exposures to influence patient susceptibility to the diseases as well as clinical outcomes, such as survival and recurrence. We aimed to identify genetic prognostic markers for non-small cell lung cancer (NSCLC), a major (85%) subtype of lung cancer, and also in other subgroups. With the fast evolution of genotyping technology, genetic association studies have went through candidate gene approach, to pathway-based approach, to the genome wide association study (GWAS). Even in the era of GWAS, pathway-based approach has its own advantages on studying cancer clinical outcomes: it is cost-effective, requiring a smaller sample size than GWAS easier to identify a validation population and explore gene-gene interactions. In the current study, we adopted pathway-based approach focusing on two critical pathways - miRNA and inflammation pathways. MicroRNAs (miRNA) post-transcriptionally regulate around 30% of human genes. Polymorphisms within miRNA processing pathways and binding sites may influence patients’ prognosis through altered gene regulation. Inflammation plays an important role in cancer initiation and progression, and also has shown to impact patients’ clinical outcomes. We first evaluated 240 single nucleotide polymorphisms (SNPs) in miRNA biogenesis genes and predicted binding sites in NSCLC patients to determine associations with clinical outcomes in early-stage (stage I and II) and late-stage (stage III and IV) lung cancer patients, respectively. First, in 535 early-stage patients, after correcting multiple comparisons, FZD4:rs713065 (hazard ratio [HR]:0.46, 95% confidence interval [CI]:0.32-0.65) showed a significant inverse association with survival in early stage surgery-only patients. SP1:rs17695156 (HR:2.22, 95% CI:1.44-3.41) and DROSHA:rs6886834 (HR:6.38, 95% CI:2.49-16.31) conferred increased risk of progression in the all patients and surgery-only populations, respectively. FAS:rs2234978 was significantly associated with improved survival in all patients (HR:0.59, 95% CI:0.44-0.77) and in the surgery plus chemotherapy populations (HR:0.19, 95% CI:0.07-0.46).. Functional genomics analysis demonstrated that this variant creates a miR-651 binding site resulting in altered miRNA regulation of FAS, providing biological plausibility for the observed association. We then analyzed these associations in 598 late-stage patients. After multiple comparison corrections, no SNPs remained significant in the late stage group, while the top SNP NAT1:rs15561 (HR=1.98, 96%CI=1.32-2.94) conferred a significantly increased risk of death in the chemotherapy subgroup. To test the hypothesis that genetic variants in the inflammation-related pathways may be associated with survival in NSCLC patients, we first conducted a three-stage study. In the discovery phase, we investigated a comprehensive panel of 11,930 inflammation-related SNPs in three independent lung cancer populations. A missense SNP (rs2071554) in HLA-DOB was significantly associated with poor survival in the discovery population (HR: 1.46, 95% CI: 1.02-2.09), internal validation population (HR: 1.51, 95% CI: 1.02-2.25), and external validation (HR: 1.52, 95% CI: 1.01-2.29) population. Rs2900420 in KLRK1 was significantly associated with a reduced risk for death in the discovery (HR: 0.76, 95% CI: 0.60-0.96) and internal validation (HR: 0.77, 95% CI: 0.61-0.99) populations, and the association reached borderline significance in the external validation population (HR: 0.80, 95% CI: 0.63-1.02). We also evaluated these inflammation-related SNPs in NSCLC patients in never smokers. Lung cancer in never smokers has been increasingly recognized as distinct disease from that in ever-smokers. A two-stage study was performed using a discovery population from MD Anderson (411 patients) and a validation population from Mayo Clinic (311 patients). Three SNPs (IL17RA:rs879576, BMP8A:rs698141, and STK:rs290229) that were significantly associated with survival were validated (pCD74:rs1056400 and CD38:rs10805347) were borderline significant (p=0.08) in the Mayo Clinic population. In the combined analysis, IL17RA:rs879576 resulted in a 40% reduction in the risk for death (p=4.1 × 10-5 [p=0.61, heterogeneity test]). We also validated a survival tree created in MD Anderson population in the Mayo Clinic population. In conclusion, our results provided strong evidence that genetic variations in specific pathways that examined (miRNA and inflammation pathways) influenced clinical outcomes in NSCLC patients, and with further functional studies, the novel loci have potential to be translated into clinical use.

Genetic variants within the Wnt/ B-catenin signaling pathway as indicators of bladder cancer clinical outcomes

The genetic factors that influence bladder cancer clinical outcomes are largely unknown. In this clinical outcomes study, I assessed genetic variations in the Wnt/β-catenin stem-cell pathway genes for association with recurrence and progression. A total of 230 SNPS in 40 genes from the Wnt/β-catenin pathway were genotyped in 419 histologically confirmed non-muscle invasive bladder cancer cases. Several significant associations were observed in the clinical outcomes analysis. Under the dominant model WNT8B: rs4919464 (HR: 1.55, 95% CI: 1.17-2.06, P=2.2x10-3) and WNT8B: rs3793771 (HR: 1.54, 95% CI: 1.09-1.62, P=4.6x10-3 ) were statistically significantly associated with an increase risk of recurrence while two other variants, APC2: rs11668593 (HR: 2.50, 95% CI: 1.43-4.35, P=1.2x10-3) and LRP5 : rs312778 (HR: 1.81, 95% CI: 1.23-2.65, P=2.7x10-3), were significantly associated with recurrence risk under the recessive model of inheritance. Four SNPs in the recessive model were associated with an increased risk of progression (AXIN2: rs1544427, LRP5: rs312778, AXIN1: rs370681, AXIN1: rs2301522). LRP5: rs312778 had the most significant increased risk of progression with a 2.68 (95% CI: 1.52-4.72, P=6.4x10-4)-fold increased risk. Stratification analysis based on treatment regimen (transurethral resection (TUR) and Bacillus Calmette-Guérin (BCG)) was also performed. Individuals with at least one variant in AXIN2: rs2007085 were found to have a 2.09 (95% CI: 1.24-3.52, P=5.4x10-3) -fold increased risk of recurrence in those that received TUR only, and no statistically significant effect was seen in those that received BCG. Individuals who received TUR with at least one variant in LEF1: rs10516550 were found to have a 2.26 (95% CI: 1.22-4.18, P=9.7x10-3)-fold increase risk of recurrence and no statistically significant effect was found in individuals who received BCG. Also, the recessive model of LRP6: rs2302684 in TUR only treatment was shown to have a 1.95 (95%CI: 1.18-3.21, P=8.8x10 -3)-fold increased risk of recurrence, and a suggested protective effect associated with a (HR: 0.83, 95% CI: 0.51-1.37, P=0.468) decreased risk of recurrence. Together, these findings implicate the Wnt/β-catenin stem-cell pathway as playing a role in bladder cancer clinical outcomes and have important implications for personalization of future treatment regimens. ^

Chlorine stable isotopic composition of basement fluids from ODP Leg 168 sites

This paper presents chlorine stable isotope compositions (delta37Cl) of sediment pore waters collected by squeezing sediment cores from the sediment-basement interface along an East-West transect through the eastern flank of the Juan de Fuca Ridge (ODP Leg 168). These "near basement fluids" (NBF) are generally thought to be representative of low-temperature fluids circulating in the off-axis basaltic crust. The delta37Cl value of the fluid directly sampled from a flow at the base of Site 1026 (WSTP1026) is also reported. NBF display delta37Cl values between -2.09? and -0.12? relative to the Standard Mean Ocean Chloride (SMOC defined as 0?) and small variations in chlorinity (~4%). These data contrast with the homogeneity of delta37Cl values associated with highly variable chlorinities observed in high-temperature on-axis fluids [Bonifacie et al., 2005, doi:10.1016/j.chemgeo.2005.06.008]. The NBF delta37Cl values show a general decreasing trend with distance from the ridge-axis except for two fluids. When plotted against delta18O values, the delta37Cl of the NBF show two different trends. This paper discusses the possible contributions on NBF delta37Cl values of fluid-mixing, water-rock interactions and transport processes (diffusion, ion membrane filtration) that can occur in the igneous basement. However, as none of these processes can fully explain the observed delta37Cl variations, the potential effect of the sediment cover is also investigated. At site 1026, the interstitial pore fluid displays a delta37Cl signature significantly lower than that of the fluid discharge sample (-1.90? and -0.28?, respectively). This difference, demonstrated here cannot be an artifact of the sampling method, rather indicates the influence of the sediment cover on NBF delta37Cl values. The potential contributions of physical processes associated with transport/compaction (e.g., diffusion, ion membrane filtration, adsorption, ion exchange) on NBF delta37Cl values are qualitatively discussed here but require additional studies for further insights. However, this study indicates that "near basement fluids" (NBF) are not, at least for Cl isotopic compositions, necessarily as representative of fluids circulating in the basaltic crust as initially thought. These results add new constraints on Cl geodynamics and show that Cl-isotopes fractionate during low-temperature circulation of fluids in off-axis and off-margin flow contexts, but not to the extent observed for active margins. Fluids circulating at low-temperature in the magmatic and/or the sedimentary part of the oceanic crust might have played a major role on the delta37Cl evolution of seawater over geologic time.

Modelización de la fenología del haba cv. Alameda

La predicción de la fenología del haba es un paso crítico para optimizar el manejo de los cultivos, así como para el desarrollo de modelos de cultivos. Este artículo examina la respuesta fenológica del cultivo de haba (Vicia faba L.) a diversos regímenes térmicos y fotoperíodicos evaluada mediante modelos lineales. Se realizaron diecisiete fechas de siembra durante tres años en Lugo, España (43°04’ N; 7°30’ W; altitud 480 m) en las que se hicieron observaciones fenológicas. El tiempo desde emergencia a floración se describe satisfactoriamente mediante un modelo fototérmico. Las tasas de desarrollo de siembra a emergencia, floración hasta la primera vaina y primera vaina hasta madurez fisiológica fueron modeladas en forma satisfactoria, utilizando solamente la temperatura como variable independiente. Los valores de temperaturas basales variaron entre 2,09 y 4,47°C, dependiendo del subperíodo fenológico. El fotoperíodo base resultó de 6,9 h mientras el fotoperíodo crítico fue de 16,2 h.